Wishaw Hospital, Department of Respiratory Medicine, 50 Netherton Road, Wishaw, Lanarkshire ML2 0DP, UK.
Expert Opin Pharmacother. 2012 May;13(7):1069-75. doi: 10.1517/14656566.2012.662221. Epub 2012 Feb 25.
Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder associated with considerable morbidity and mortality. β2-adrenoceptor agonists (β2-agonists) act by stimulating the β2-adrenoceptor present on smooth muscle and other cells in the airways, resulting in bronchodilatation. β2-agonists play a central role in the treatment of breathlessness in patients with COPD. Salbutamol is a chiral drug with (R)- and (S)- isomers. Almost all β2-agonists that are currently used are racemic mixtures of (R)- and (S)-salbutamol.
(R)-salbutamol alone (Xenopex®, generically known as levosalbutamol) is now indicated for the treatment or prevention of bronchospasm with reversible obstructive airway disease. This evaluation demonstrates that (R)-salbutamol provides a beneficial β2-agonist effect at a cellular level and in experimental models of airways disease. Furthermore, we demonstrate that (S)-salbutamol opposes the desirable effects of (R)-salbutamol and can actually cause features of asthma and COPD in vitro and in experimental asthma.
Despite this strong body of preclinical experimental evidence, (R)-salbutamol has not shown consistent superiority over (S)- or racemic salbutamol in the treatment of patients with COPD.
慢性阻塞性肺疾病（COPD）是一种与高发病率和死亡率相关的炎症性疾病。β2-肾上腺素能受体激动剂（β2-agonists）通过刺激气道平滑肌和其他细胞上存在的β2-肾上腺素能受体而起作用，导致支气管扩张。β2-agonists 在 COPD 患者呼吸困难的治疗中起着核心作用。沙丁胺醇是一种手性药物，具有（R）-和（S）-异构体。目前使用的几乎所有β2-agonists 都是（R）-和（S）-沙丁胺醇的外消旋混合物。
（R）-沙丁胺醇单独（Xenopex®，通常称为左沙丁胺醇）现已被用于治疗或预防具有可逆性气道阻塞性疾病的支气管痉挛。这项评估表明，（R）-沙丁胺醇在细胞水平和气道疾病的实验模型中提供了有益的β2-激动剂作用。此外，我们证明（S）-沙丁胺醇拮抗（R）-沙丁胺醇的理想作用，实际上可以在体外和实验性哮喘中引起哮喘和 COPD 的特征。
尽管有大量的临床前实验证据，但（R）-沙丁胺醇在治疗 COPD 患者方面并未显示出比（S）-或外消旋沙丁胺醇更一致的优势。
